The effectiveness of chemotherapy for anticancer treatment purposes has been largely restricted by its harmful side effects caused by a lack of selectivity and difficulty in treatment monitoring. One of the most promising enhancements of cancer treatment is the development of selective drug delivery mechanisms that are capable of releasing treatments in response to individual tumor microenvironments. A promising potential mechanism for specific drug delivery is glutathione (GSH)-mediated prodrug activation. In normal cells, glutathione is an important antioxidant that prevents oxidative stress to various parts of the cell. Cancer cells have a 30-40 times greater glutathione concentration than healthy cells. Various prodrug systems have been developed that release treatment drugs in response to glutathione. However, few mechanisms have been developed that can effectively monitor the release of such treatments after stimulation by GSH.
Theranostic prodrugs, equipped with both fluorophoric biomarkers and small molecule drugs, are designed to improve drug delivery monitoring due to their ability to concurrently release their biomarker and drug constituents. However, most of the fluorophores used as theranostic prodrugs suffer from short wavelength emission, tissue autofluorescence interference, and photoinstabilities.